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Record W2896104537 · doi:10.1073/pnas.1804003115

Translating biased signaling in the ghrelin receptor system into differential in vivo functions

2018· article· en· W2896104537 on OpenAlexafffund
Franziska Mende, Cecilie Hundahl, Bianca Plouffe, Louise J. Skov, Andreas Nygaard Madsen, Michael Lückmann, Thi Ai Diep, Stefan Offermanns, Thomas M. Frimurer, Michel Bouvier, Birgitte Holst

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2018
Typearticle
Languageen
FieldNeuroscience
TopicRegulation of Appetite and Obesity
Canadian institutionsUniversité de MontréalInstitute for Research in Immunology and Cancer
FundersNovo NordiskDet Sundhedsvidenskabelige Fakultet, Københavns UniversitetDiabetes CanadaLundbeckfondenNovo Nordisk FondenNovo Nordisk Foundation Center for Basic Metabolic ResearchFaculty of Health and Medical Sciences, University of Western Australia
KeywordsGhrelinIn vivoDifferential (mechanical device)ReceptorCell biologyChemistrySignal transductionBiologyNeuroscienceComputational biologyBiochemistryPhysicsGeneticsThermodynamics

Abstract

fetched live from OpenAlex

Significance Obesity is a major health threat of the twenty-first century, impacting individual patients and healthcare expenditure. Due to safety concerns, few antiobesity treatments with only moderate effect remain on the market. The ghrelin receptor is an attractive target for the development of novel antiobesity drugs, since ghrelin increases both fat accumulation and food intake. However, ghrelin also modulates a variety of additional physiological functions. Thus, drugs targeting the ghrelin receptor may induce unacceptable side effects and have limited clinical use. We demonstrate that biased ligands, which selectively activate only a subset of the molecular signaling pathways, may be powerful tools to obtain drugs that efficaciously reduce body weight without inducing adverse effects by selectively modulating appetite and energy expenditure.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.023
Threshold uncertainty score0.268

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.057
GPT teacher head0.301
Teacher spread0.244 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations67
Published2018
Admission routes2
Has abstractyes

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